Cross-Dressing of Multiple Myeloma Cells Mediated by Extracellular Vesicles Conveying MIC and ULBP Ligands Promotes NK Cell Killing
Natural Killer (NK) cells are innate cytotoxic lymphoid cells that play a crucial role in cancer immunosurveillance. NKG2D is an activating receptor that binds to MIC and ULBP molecules typically induced on damaged, transformed, or infected cells. The secretion of NKG2D ligands (NKG2DLs) through pro...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/11/9467 |
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| author | Elisabetta Vulpis Luisa Loconte Chiara Cassone Fabrizio Antonangeli Giulio Caracciolo Laura Masuelli Francesca Fazio Maria Teresa Petrucci Cinzia Fionda Alessandra Soriani Cristina Cerboni Marco Cippitelli Angela Santoni Alessandra Zingoni |
| author_facet | Elisabetta Vulpis Luisa Loconte Chiara Cassone Fabrizio Antonangeli Giulio Caracciolo Laura Masuelli Francesca Fazio Maria Teresa Petrucci Cinzia Fionda Alessandra Soriani Cristina Cerboni Marco Cippitelli Angela Santoni Alessandra Zingoni |
| author_sort | Elisabetta Vulpis |
| collection | DOAJ |
| description | Natural Killer (NK) cells are innate cytotoxic lymphoid cells that play a crucial role in cancer immunosurveillance. NKG2D is an activating receptor that binds to MIC and ULBP molecules typically induced on damaged, transformed, or infected cells. The secretion of NKG2D ligands (NKG2DLs) through protease-mediated cleavage or in an extracellular vesicle (EV) is a mode to control their cell surface expression and a mechanism used by cancer cells to evade NKG2D-mediated immunosurveillance. EVs are emerging as important players in mediating cell-to-cell communication due to their ability to transfer biological material to acceptor cells. Herein, we investigated the spreading of NKG2DLs of both MIC and ULBP molecules through the EV-mediated cross-dressing on multiple myeloma (MM) cells. We focused our attention on two MICA allelic variants, namely MICA*008 and MICA*019, representing the prototype of short and long MICA alleles, respectively, and on ULBP-1, ULBP-2, and ULBP-3. Our findings demonstrate that both ULBP and MICA ligands can be acquired from tumor cells through EVs enhancing NK cell recognition and killing. Moreover, besides MICA, EVs expressing ULBP-1 but not ULBP-2 and 3 were detected in bone marrow aspirates derived from a cohort of MM patients. Our findings shed light on the role of EV-associated MICA allelic variants and ULBP molecules in the modulation of NKG2D-mediated NK cell immunosurveillance in the tumor microenvironment. Moreover, the EV-mediated transfer of NKG2DLs could suggest novel therapeutic approaches based on the usage of engineered nanoparticles aimed at increasing cancer cell immunogenicity. |
| first_indexed | 2024-03-11T03:05:36Z |
| format | Article |
| id | doaj.art-554f01c0d85d4df283ff6af925ac9a69 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:05:36Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-554f01c0d85d4df283ff6af925ac9a692023-11-18T07:59:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012411946710.3390/ijms24119467Cross-Dressing of Multiple Myeloma Cells Mediated by Extracellular Vesicles Conveying MIC and ULBP Ligands Promotes NK Cell KillingElisabetta Vulpis0Luisa Loconte1Chiara Cassone2Fabrizio Antonangeli3Giulio Caracciolo4Laura Masuelli5Francesca Fazio6Maria Teresa Petrucci7Cinzia Fionda8Alessandra Soriani9Cristina Cerboni10Marco Cippitelli11Angela Santoni12Alessandra Zingoni13Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Molecular Medicine, “Sapienza” University of Rome, 00185 Rome, ItalyLaboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Molecular Medicine, “Sapienza” University of Rome, 00185 Rome, ItalyLaboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Molecular Medicine, “Sapienza” University of Rome, 00185 Rome, ItalyInstitute of Molecular Biology and Pathology, National Research Council (CNR), 00185 Rome, ItalyDepartment of Molecular Medicine, “Sapienza” University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, “Sapienza” University of Rome, 00161 Rome, ItalyDepartment of Cellular Biotechnologies and Hematology, “Sapienza” University of Rome, 00161 Rome, ItalyDepartment of Cellular Biotechnologies and Hematology, “Sapienza” University of Rome, 00161 Rome, ItalyLaboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Molecular Medicine, “Sapienza” University of Rome, 00185 Rome, ItalyLaboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Molecular Medicine, “Sapienza” University of Rome, 00185 Rome, ItalyLaboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Molecular Medicine, “Sapienza” University of Rome, 00185 Rome, ItalyLaboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Molecular Medicine, “Sapienza” University of Rome, 00185 Rome, ItalyLaboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Molecular Medicine, “Sapienza” University of Rome, 00185 Rome, ItalyLaboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Molecular Medicine, “Sapienza” University of Rome, 00185 Rome, ItalyNatural Killer (NK) cells are innate cytotoxic lymphoid cells that play a crucial role in cancer immunosurveillance. NKG2D is an activating receptor that binds to MIC and ULBP molecules typically induced on damaged, transformed, or infected cells. The secretion of NKG2D ligands (NKG2DLs) through protease-mediated cleavage or in an extracellular vesicle (EV) is a mode to control their cell surface expression and a mechanism used by cancer cells to evade NKG2D-mediated immunosurveillance. EVs are emerging as important players in mediating cell-to-cell communication due to their ability to transfer biological material to acceptor cells. Herein, we investigated the spreading of NKG2DLs of both MIC and ULBP molecules through the EV-mediated cross-dressing on multiple myeloma (MM) cells. We focused our attention on two MICA allelic variants, namely MICA*008 and MICA*019, representing the prototype of short and long MICA alleles, respectively, and on ULBP-1, ULBP-2, and ULBP-3. Our findings demonstrate that both ULBP and MICA ligands can be acquired from tumor cells through EVs enhancing NK cell recognition and killing. Moreover, besides MICA, EVs expressing ULBP-1 but not ULBP-2 and 3 were detected in bone marrow aspirates derived from a cohort of MM patients. Our findings shed light on the role of EV-associated MICA allelic variants and ULBP molecules in the modulation of NKG2D-mediated NK cell immunosurveillance in the tumor microenvironment. Moreover, the EV-mediated transfer of NKG2DLs could suggest novel therapeutic approaches based on the usage of engineered nanoparticles aimed at increasing cancer cell immunogenicity.https://www.mdpi.com/1422-0067/24/11/9467extracellular vesiclesNKG2Dnatural killer cellsmultiple myeloma |
| spellingShingle | Elisabetta Vulpis Luisa Loconte Chiara Cassone Fabrizio Antonangeli Giulio Caracciolo Laura Masuelli Francesca Fazio Maria Teresa Petrucci Cinzia Fionda Alessandra Soriani Cristina Cerboni Marco Cippitelli Angela Santoni Alessandra Zingoni Cross-Dressing of Multiple Myeloma Cells Mediated by Extracellular Vesicles Conveying MIC and ULBP Ligands Promotes NK Cell Killing International Journal of Molecular Sciences extracellular vesicles NKG2D natural killer cells multiple myeloma |
| title | Cross-Dressing of Multiple Myeloma Cells Mediated by Extracellular Vesicles Conveying MIC and ULBP Ligands Promotes NK Cell Killing |
| title_full | Cross-Dressing of Multiple Myeloma Cells Mediated by Extracellular Vesicles Conveying MIC and ULBP Ligands Promotes NK Cell Killing |
| title_fullStr | Cross-Dressing of Multiple Myeloma Cells Mediated by Extracellular Vesicles Conveying MIC and ULBP Ligands Promotes NK Cell Killing |
| title_full_unstemmed | Cross-Dressing of Multiple Myeloma Cells Mediated by Extracellular Vesicles Conveying MIC and ULBP Ligands Promotes NK Cell Killing |
| title_short | Cross-Dressing of Multiple Myeloma Cells Mediated by Extracellular Vesicles Conveying MIC and ULBP Ligands Promotes NK Cell Killing |
| title_sort | cross dressing of multiple myeloma cells mediated by extracellular vesicles conveying mic and ulbp ligands promotes nk cell killing |
| topic | extracellular vesicles NKG2D natural killer cells multiple myeloma |
| url | https://www.mdpi.com/1422-0067/24/11/9467 |
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